Tetrahydronaphthalene and indane derivatives

ABSTRACT

The compounds of the formula ##STR1## wherein X and Y are independently --CH 2  -- or &gt;C(CH 3 ) 2  ; Z is --CHR 8  --, &gt;CO, &gt;CR 8  OR 7 , --CHR 8  --CHR 8  --, --CHOR 7  --CH 2  --, --CO--CHOR 7  or --CHOR 7  --CHOR 7  --; R 1  is a 5- or 6-membered, monocyclic heterocyclic group which optionally can be C-substituted by halogen, lower-alkyl, lower-alkoxy, acyloxy, nitro, hydroxy, amino, lower-alkylamino or di-lower-alkylamino and/or which can be substituted on a ring --NH-- group by lower-alkyl; R 2  and R 3  are independently hydrogen, lower-alkyl, trifluoromethyl or halogen and one of R 2  and R 3  always is trifluoromethyl or lower-alkyl; R 4  and R 5  are independently hydrogen, alkyl, alkoxy or halogen; R 6  is hydrogen, lower-alkyl or --OR 7  ; R 7  is hydrogen, lower-alkyl or acyl; R 8  is hydrogen or lower-alkyl; and R 7  and R 8  can be the same or different from one another, 
     are useful for the treatment of neoplasms and dermatoses in mammals. The compounds can be manufactured from a corresponding bicyclic component and a heterocyclic component containing the residue R 1  by a Wittig, Horner or Grignard reaction and the optional subsequent transformation of reactive groups.

This is a division of application Ser. No. 07/072,075 filed July 10,1987, now U.S. Pat. No. 4,876,349.

DESCRIPTION OF THE INVENTION

The present invention is concerned with tetrahydronaphthalene and indanederivatives of the formula ##STR2## wherein X and Y are independently--CH₂ -- or >C(CH₃)₂ ; Z is --CHR⁸ --, >CO, >CR⁸ OR⁷, --CHR⁸ --CHR⁸ --,--CHOR⁷ --CH₂ --, --CO--CHOR⁷ or --CHOR⁷ --CHOR⁷ --; R¹ is a 5- or6-membered, monocyclic heterocyclic group which is unsubstituted or canbe C-substituted by halogen, lower-alkyl, lower-alkoxy, acyloxy, nitro,hydroxy, amino, lower-alkylamino or di-lower-alkylamino and/or which canbe substituted on a ring --NH-- group by lower-alkyl; R² and R³ areindependently hydrogen, lower-alkyl, trifluoromethyl or halogen and oneof R² and R³ is always trifluoromethyl or lower-alkyl; R⁴ and R⁵ areindependently hydrogen, alkyl, alkoxy or halogen; R⁶ is hydrogen,lower-alkyl or --OR⁷ ; R⁷ is hydrogen, lower-alkyl or acyl; R⁸ ishydrogen or lower-alkyl; and R⁷ and R⁸ can be the same or different fromone another.

The term "lower" is used throughout this description to refer to groupsor substituents having 1 to 6 carbon atoms. Alkyl and alkoxy groups canbe straight-chain or branched, such as methyl, ethyl, propyl, isopropyl,butyl, sec.-butyl and methoxy, ethoxy, propoxy, isopropoxy, butoxy andsec.-butoxy, respectively. Alkyl and alkoxy groups R⁴ and R⁵ preferablycontain up to 10 carbon atoms such as octyl, nonyl, decyl and2,2-dimethyloctyl and octyloxy, nonyloxy, decyloxy and2,2-dimethyloctyloxy, respectively. Examples of the acyloxy groups arealkanoyloxy groups, preferably lower-alkanoyloxy groups such as acetoxy,propionyloxy, butyryloxy, pivaloyloxy and caproyloxy; or aroyloxy groupssuch as benzoyloxy, p-nitrobenzoyloxy and toluoyloxy; or aralkanoyloxygroups such as phenylacetoxy. Halogen embraces fluorine, chlorine,bromine and iodine. The heterocyclic group represented by R¹ can containO, N and/or S as hereto atom(s). Examples include pyridyl, pyrimidinyl,furyl, thienyl, imidazolyl, isoxazolyl, oxazolyl and thiazolyl.

In greater detail, Examples of heterocylic group R¹ are pyridyl,especially 4-pyridyl; pyrimidinyl, especially 2- and 4-pyrimidinyl;thienyl; furyl; oxazolyl, especially 5-oxazolyl; isoxazolyl, especially5-isoxazolyl; thiazolyl, especially 5-thiazolyl; pyrrolyl, especially2-pyrrolyl; imidazolyl, especially 5-imidazolyl; and pyrazolyl,especially 5-pyrazolyl. As indicated, R¹ can be C-substituted by theaforementioned residues and/or can be substituted on a ring --NH-- groupby lower-alkyl, that is, the substituents can be present on one or morecarbon atoms or on an NH group of the heterocyclic ring, with thesubstituent on an NH group being lower-alkyl. Examples of suchsubstituted heterocyclic groups (R¹) are 3-substituted 4-pyridyl,2,4-di-substituted 3-pyridyl, 1-substituted 2-pyrrolyl and1,4-disubstituted imidazolyl.

The compounds of formula I can exist as trans or cis isomers orcis/trans isomer mixtures. In general, the trans compounds of formula Iare preferred.

Among the compounds of formula I, preferred are those in which X and Yare >C(CH₃)₂ and Z represents --CH₂ --CH₂ --. R¹ is preferably anunsubstituted heterocyclic group. With respect to R² and R³, hydrogen ispreferred for R² and lower-alkyl especially methyl, is preferred for R³.R⁴ is preferably hydrogen or alkyl or alkoxy having up to 10 carbonatoms. R⁵ and R⁶ are preferably hydrogen.

The invention is also concerned in its other aspects with a process forthe production of the compounds of formula I, pharmaceuticalcompositions based on the compounds of formula I and the use of thecompounds of formula I in the treatment or prevention of neoplasms anddermatoses.

The compounds of formula I can be manufactured in accordance with theinvention by reacting a compound of the formula ##STR3## with a compoundof the formula

    R.sup.1 --B

in which

A is --CH(R³)P⁺ (Q)₃ Y⁻ or --CH(R³)--P(O)(OAlk)₂ and B is a residue R²¹--CO--; or A is R³¹ --CO-- and B is one of --CH(R²)P⁺ (Q)₃ Y⁻.--CH(R²)--P(O)(OAlk)₂ or --CH(R²¹)MgHal; or A is --CH(R³¹)MgHal and B isR² --CO--; Q is aryl; Y⁻ is the anion of an organic or inorganic acid;Alk is a lower alkyl group; Hal is halogen; R²¹ and R³¹ are hydrogen,trifluoromethyl or lower-alkyl; and R¹, R², R³, R⁴, R⁵, X, Y and Z havethe meaning given above,

If desired, a nitro group present as a substituent in R¹ is reduced tothe amino group and, optionally, is mono- or di-alkylated, an acyloxygroup R⁷ or an acyloxy group present as a substituent in R¹ issaponified, a carbonyl group present in Z is reduced to the hydroxygroup, and a hydroxy group R⁷ or a hydroxy group present as asubstituent in R¹ or present in Z is alkylated or acylated.

The reaction of the compounds of formula II and R¹ --B can be carriedout according to the known methods of the Wittig, Horner or Grignardreaction.

In the case of the Wittig reaction, i.e. with the use of a compound offormula II with A being --CH(R³)P⁺ (Q)₃ Y⁻ or of the formula R¹ --B withB being --CH(R²)P⁺ (Q)₃ Y⁻, the components are reacted with one anotherin the presence of an acid-binding agent, for example, a strong basesuch as butyl-lithium, sodium hydride or the sodium salt of dimethylsulphoxide, and especially in the presence of an optionally loweralkyl-substituted ethylene oxide such as 1,2-butylene oxide. A reactionsolvent is optional, for example, an ether such as diethyl ether ortetrahydrofuran or in an aromatic hydrocarbon such as benzene. Thereaction is conducted at a temperature between room temperature and theboiling point of the reaction mixture.

Among the inorganic acid ions Y⁻ the chloride ion, the bromide ion orthe hydrosulphate ion is preferred, and among the organic acid ions thetosyloxy ion is preferred. The aryl group Q is preferably phenyl or asubstituted phenyl such as p-tolyl.

In the case of the Horner reaction, that is, with the use of a compoundof formula II with A being --CH(R³)--P(O)(OAlk)₂ or of the formula R¹--B with B being --CH(R²)--P(O)(OAlk)₂, the components are condensedwith the aid of a base and preferably in the presence of an inertorganic solvent, for example, with the aid of sodium hydride in benzene,toluene, dimethylformamide, tetrahydrofuran, dioxane or1,2-dimethoxyethane, or also with the aid of a sodium alcoholate in analkanol, for example, sodium methylate in methanol, at a temperaturebetween 0° and the boiling point of the reaction mixture.

The alkoxy groups OAlk are especially lower alkoxy with 1-6 carbon atomssuch as methoxy or ethoxy.

The reaction of a compound of formula II, with A being --CH(R³¹)MgHal,or of the formula R¹ --B, with B being --CH(R²¹)MgHal, can be carriedout in a manner known per se under the conditions of a Grignardreaction, for example, in an ether such as diethyl ether ortetrahydrofuran at room temperature and subsequent water-cleavage withacidic agents, for example, with organic acids such asp-toluenesulphonic acid.

Compounds of formula I which contain an amino substituent in theheterocyclic ring are conveniently prepared via the corresponding nitrocompounds. A nitro group present in a compound of formula I can beconverted into an amino group in a manner known per se by reduction, forinstance, with nascent hydrogen. An amino group present in a compound offormula I can be mono- or di-alkylated in a manner known per se, forexample, by treatment with alkylating agents such as alkyl halides oralkyl sulphates or by reductive alkylation with aldehydes such asformaldehyde or acetaldehyde and sodium cyanoborohydride. The reductionof a carbonyl group present in Z as well as the alkylation and acylationof hydroxy groups can also be carried out in a manner known per se. Forexample, a carbonyl group can be reduced to the hydroxy group bytreatment with reduction agent such as sodium borohydride.

As indicated, the compounds of formula I can exist in trans or cis form.In the process described above they are mainly obtained in the transform. Cis components which may be obtained can be separated, if desired,in a manner known per se.

The starting materials of formula II and R¹ --B, insofar as theirpreparation is not known or is not described hereinafter, can beprepared in analogy to known methods or to methods describedhereinafter.

The compounds of formula I are therapeutically active. In particular,they possess anti-seborrhoeic, anti-keratinizing, anti-neoplastic andanti-allergic/anti-inflammatory activity, which can be demonstratedusing the test procedures described hereinafter: A) Theanti-keratinizing activity can be determined on the rhino mouse modelaccording to the following procedure. The skin of the rhino mouse ischaracterized by the presence of keratin-filled utriculi of theepidermis and subcutaneous cysts, both of which are derived from hairfollicles. The administration of retinoids leads to a hyperproliferationof the epidermis and of the epithelium lining of the utriculi. Thethickening of the epidermis and the reduction in the size of theutriculi lead to a normalization of the altered structure of theepithelium layer. The daily topical application, to the skin of therhino mouse, of a 3% acetone solution of an active test compound in anamount of 0.1 ml/cm² over-a period of 3 weeks, or the thrice weekly oraladministration of the active test compound in arachis oil over a periodof 3 weeks, leads to a significant proliferation of the epidermis and astriking reduction of the keratin-filled utriculi. B) The activity inthe prevention of chemically-induced breast tumors can be determinedaccording to the following Procedure. Female Sprague-Dawley rats arekept under temperature-controlled and light-controlled conditions, withfree access to drinking water and feed. At the age of 50 days 15 mg ofdimethylbenz(a)anthracene dissolved in arachis oil are administered toeach rat by means of a probang. The treatment with the test compoundsbegins 1 day after the administration of the carcinogen. The bodyweights of the test animals are recorded and the tumors are palpatedweekly and measured with a vernier caliper. The volumes are calculatedaccording to the formula D/2·d² in which D represents the largerdiameter of the tumor ellipsoid and d represents the smaller diameter ofthe tumor ellipsoid. After 11 weeks the test is terminated andevaluated. In this test there are used in addition to 30 controlanimals, which receive exclusively normal feed, the following two groupsof rest animals:

1. 33 rats to which are administered daily 30 mg/kg of test compoundmixed with the feed; and

2. 36 rats to which are administered daily 90 mg/kg of test compoundmixed with the feed. C) The activity on tumors can be determined on thetransplantable chondrosarcoma of the rat according to the followingmethod. The solid tumor of a donor animal is finely minced and suspendedin phosphate buffer/sodium chloride solution. Thereafter 0.5 ml of the30% tumor suspension is implanted subcutaneously into albino rats.

The transplanted rats are divided into test groups of 8 animals each.The test compounds are suspended in arachis oil and administered orallyfive times per week for 24 days. The tumors are excised and weighed onday 24. The results are expressed in the quotient C/T which iscalculated as follows: ##EQU1## D) The antimetaplastic activity can alsobe determined in rats according to the following method. FemaleHoltzmann rats weighing approximately 100 g are ovarectomized underThiogenal narcosis after an adaptation period of 8 days and are used inthe test after a further 14 days. In each case two animals are placed ina cage with free access to feed which contains approximately 2000 IU ofvitamin A determined analytically. Prior to the oral administration ofthe test compound the animals are treated subcutaneously each day on 6successive days with 1 μg of estradiol benzoate and 250 μg oftestosterone propionate dissolved in 0.1 ml of sesame oil. Theparenteral hormone administration leads to the formation of a cleargranular stage in the vaginal smear, that is, a squamous, metaplasia.Two days after the oral administration of the test substance the resultof the reaction is again read off on the vaginal epithelium. The areamethod according to Behrens and Karber is employed to calculate theaverage effective dosages.

E) The activity of the compounds I on sebum secretion in rats wasdetermined according to the following procedure. Male rats ofapproximately 50-60 g body weight were castrated at the age of 21-22days. One week after this operation the rats were washed in a cleansingsolution in order to remove sebum which was excreted prior to the testperiod. Only the carrier materials used were administered to one groupof rats. A further group of rats also simultaneously received 100 μg oftestosterone propionate in 0.2 ml of sesame oil per rat per day. To afurther group of rats there were administered daily per rat 100 μg oftestosterone propionate in 0.2 ml of sesame oil subcutaneously and thetest compounds in various dosages in 0.2 ml of propylene glycol orally.The rats were treated in this manner for 14 days. On the 15th day thesebum from the skin surface and the pelt was removed by immersing theentire body of the test animals in a determined volume of acetone andbathing therein for 2 minutes. An aliquot of the solvent bath wasevaporated and the solid residue was determined, gravimetrically. Theinhibition of the testosterone-stimulated increase in the serumsecretion in comparison to the corresponding values from rats treatedonly with testosterone propionate was used as the measurement for theactivity.

The compounds of formula I are useful in mammals for the topical andsystemic therapy of benign and malignant neoplasms, of premalignantlesions and also for the systemic and topical prophylaxis of the saidconditions.

Furthermore, they are useful in mammals for the topical and systemictherapy of acne, psoriasis and other dermatoses which are accompanied byan intensified or pathologically altered conification, as well as ofinflammatory and allergic dermatological conditions. Further, thecompounds of formula I can also be used for the control of mucousmembrane disorders with inflammatory or-degenerative or metaplasticchanges in such species.

The pharmaceutical preparations can be administered enterally,parenterally or topically. Suitable for enteral administration arepreparations in the form of tablets, capsules, dragees, syrups,suspensions, solutions and suppositories. preparations in the form ofinfusion of injection solutions are suitable for parenteraladministration.

The dosages in which the preparations are administered can varyaccording to the mode of use and route of use as well as according tothe requirements of the patients. In general, daily doses of about0.1-50 mg/kg, preferably 1-15 mg/kg, are suitable adults.

The preparations can be administered in one dosage or several dosages.Capsules containing about 5-200 mg of active substance are a preferredform.

The preparations can contain inert or pharmaco-dynamically activeadditives. Tablets or granulates can contain a series of binding agents,filler materials, carrier substances or diluents. Liquid preparationscan be present, for example, in the form of the sterile solution whichis miscible with water. Capsules can contain a filler material orthickening agent in addition to the active substance. Furthermore,flavor-improving additives as well as the substances usually used aspreserving, stabilizing, moisture-retaining and emulsifying agents,salts for varying the osmotic pressure, buffers and other additives canalso be present.

The previously mentioned carrier substances and diluents can be organicor inorganic substances, for example, water, gelatin, lactose, starch,magnesium stearate, talc, gum arabic, polyalkylene glycols, and thelike. It is a prerequisite that all adjuvants used in the production ofthe preparations be non-toxic.

For topical use the active substances are conveniently used in the formof salves, tinctures, creams, solutions, lotions, sprays, suspensionsand the like. Salves and creams as well as solutions are preferred.These preparations intended for topical use can be manufactured bymixing the compounds of formula I as active ingredients with non-toxic,inert, solid or liquid carriers which are conventional for suchpreparations and which are suitable for topical treatment.

Suitable for topical use are solutions containing 0.1-5%, preferably0.3-2%, of the active substance and salves or creams containing 0.1-5%,preferably about 0.2-2%, of the active substance.

If desired, the pharmaceutical preparations can contain an antioxidant,for example, tocopherol, N-methyl-γ-tocopheramine, butylatedhydroxyanisole or butylated hydroxytoluene.

The following Example illustrates the preparation of a compound of theinvention further. The temperatures are given in degrees Celsius.

EXAMPLE

378 g of[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]triphenylphosphoniumbromide were suspended in 4 l of butylene oxide. After the addition of51 ml of 4-pyridinecarbaldehyde the mixture was boiled at reflux for 1.5hours. After cooling the majority of the solvent was evaporated in awater-jet vacuum, the residue was poured into 1.5 l of a methanol/watermixture (ratio 6:4) and extracted repeatedly with hexane. The organicphase was washed three times with water and, after drying over sodiumsulphate, evaporated. After flash chromatography (eluting agenthexane/ether=2:1) and recrystallization from hexane there were obtained216 g of 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthyl)propenyl]pyridine in colorless crystals, melting point 84°-85°.

Analogously there were obtained the following additional compounds inaccordance with the present invention:

3-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthyl)propenyl]pyridine, melting point 93°-95°,

2-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]pyridine, melting point 77°-79°,

2-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiophene, melting point 52°-54°,

3-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiophene, melting point 80°-82°,

2-[(E)-2-(5,6,7,8-tetrahydro, 5,5,8,8,-tetramethyl-2-naphthyl)propenyl]furan, melting point 52°-54°.

4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]pyrimidine, melting point 114°.

We claim:
 1. A compound of the formula ##STR4## wherein X and Y areindependently --CH₂ -- or >(CH₃)₂ ; Z is --CHR⁸ --, or --CHR⁸ --CHR⁸ -;R¹ is thienyl which is unsubstituted or can be C-substituted by halogen,lower-alkyl, lower-alkoxy, acyloxy, nitro, hydroxy, amino,lower-alkylamino or di-lower-alkylamino; R² and R³ are independentlyhydrogen, lower-alkyl, trifluoromethyl or halogen and one of R² and R³is always trifluoromethyl or lower-alkyl; R⁴ and R⁵ are independentlyhydrogen, alkyl, alkoxy or halogen; R⁶ is hydrogen, lower-alkyl or aresidue --OR⁷ ; R⁷ is hydrogen, lower-alkyl or acyl; R⁸ is hydrogen orlower-alkyl; and R⁷ and R⁸ can be the same or different from oneanother.
 2. The compound in accordance with claim 1 in which X and Y are>C(CH₃)₂ ; Z is --CH₂ --CH₂ --; R¹ is unsubstituted thienyl; R², R⁵ andR⁶ are hydrogen; and R⁴ is hydrogen and alkyl or alkoxy having up to 10carbon atoms.
 3. The compound of claim 2,3-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiopene.
 4. The compound of claim1, 2-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiopene.
 5. Aprocess for producing a compound of the formula: ##STR5## wherein X andY are independently --CH₂ -- or >(CH₃)₂ ; Z is --CHR⁸ --, [>CO, >CR⁸OR⁷,] or --CHR⁸ --CHR⁸ --[, --CHOR⁷ --CH₂ --, --CO--CHOR⁷ or --CHOR⁷--CHOR² --]; R¹ is [a 5- or 6-membered, monocyclic heterocyclic group]thienyl which is unsubstituted or can be C-substituted by halogen,lower-alkyl, lower-alkoxy, acyloxy, nitro, hydroxy, amino,lower-alkylamino or di-lower-alkylamino; R² and R³ are independentlyhydrogen, lower-alkyl, trifluoromethyl or halogen and one of R² and R³is always trifluoromethyl or lower-alkyl; R⁴ and R⁵ are independentlyhydrogen, alkyl, alkoxy or halogen; R⁶ is hydrogen, lower-alkyl or aresidue --OR⁷ ; R⁷ is hydrogen, lower-alkyl or acyl; R⁸ is hydrogen orlower-alkyl; and R⁷ and R⁸ can be the same or different from oneanother, which process comprises reacting a compound of the formula##STR6## with a compound of the formula

    R.sup.1 --B

in whichA is --CH(R³)P⁺ (Q)₃ Y⁻ or --CH(R³)--P(O)(OAlk)₂ and B is R²¹--CO--; or A is R³¹ --CO-- and B is one of --CH(R²)P⁺ (Q)₃ Y⁻ or--CH(R²)--P(O)(OAlk)₂ or --CH(R²¹)MgHal; or A is --CH(R³¹)MgHal and B isR² --CO--; Q is aryl; Y⁻ is the anion of an organic or inorganic acid;Alk is a lower alkyl group; Hal is halogen; R²¹ and R³¹ are hydrogen,trifluoromethyl or lower-alkyl; and R¹, R², R³, R⁴, R⁵, X, Y and Z havethe same meanings as above.
 6. The process in accordance with claim 5 inwhich X and Y are >C(CH₂)₂ ; Z is --CH₂ --CH₂ --; R¹ is unsubstitutedthienyl; R², R⁵, and R⁶ are hydrogen; and R⁴ is hydrogen or alkyl oralkoxy having up to 10 carbon atoms.
 7. A pharmaceutical compositioncomprising as the active substance a compound of the formula ##STR7##wherein X and Y are independently --CH₂ -- or >C(CH₃)₂ ; Z is --CHR⁸ --,[>CO, >CR⁸ OR⁷,] or --CHR⁸ --CHR⁸ -[, --CHOR⁷ --CH₂ --, --CO--CHOR⁷ or--CHOR⁷ --CHOR⁷ ]; R¹ is thienyl which is unsubstituted or can beC-substituted by halogen, lower-alkyl, lower-alkoxy, acyloxy, nitro,hydroxy, amino, lower-alkylamino or di-lower-alkylamino; R² and R³ areindependently hydrogen, lower-alkyl, trifluoromethyl or halogen and oneof R² and R³ is always trifluoromethyl or lower-alkyl; R⁴ and R⁵ areindependently hydrogen, alkyl, alkoxy, or halogen, R⁶ is hydrogen,lower-alkyl or a residue --OR⁷ ; R⁷ is hydrogen, lower-alkyl or acyl; R⁸is hydrogen or lower-alkyl; and R⁷ and R⁸ can be the same or differentfrom one another,and a pharmaceutically acceptable carrier.
 8. Thecomposition in accordance with claim 7, in which for the compound offormula I, X and Y are >C(CH₃)₂ ; Z is --CH₂ --CH₂ --; R¹ isunsubstituted thienyl; R², R⁵ and R⁶ are hydrogen; and R⁴ is hydrogen oralkyl or alkoxy having up to 10 carbon atoms.
 9. The composition ofclaim 7, wherein the compound of formula I is selected from the groupconsisting of2-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiopene and3-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiopene.
 10. A method for treating neoplasms and dermatose inmammals which comprises administering an effective amount of apharmaceutical composition containing a compound of the formula;##STR8## wherein X and Y are independently --CH₂ --or >C(CH₃)₂ ; Z is--CHR⁸ --, [>CO, >CR⁸ OR⁷,] or --CHR⁸ --CHR⁸ -[, --CHOR⁷ --CH₂ --,--CO--CHOR⁷ or --CHOR⁷ --CHOR⁷ --]; R¹ is thienyl which is unsubstitutedor can be C-substituted by halogen, lower-alkyl, lower-alkoxy, acyloxy,nitro, hydroxy, amino, lower-alkylamino or di-lower-alkylamino; R² andR³ are independently hydrogen, lower-alkyl, trifluoromethyl or halogenand one of R² and R³ is always trifluoromethyl or lower-alkyl; R⁴ and R⁶are independently hydrogen, alkyl, alkoxy, or halogen; R⁶ is hydrogen,lower-alkyl, or a residue --OR⁷ ; R⁷ is hydrogen, lower-alkyl or acyl,R⁸ is hydrogen or lower-alkyl; and R⁷ and R⁸ can be the same ordifferent from one another,and a pharmaceutically acceptable carrier.11. The method in accordance with claim 10, in which for the compound offormula I, X and Y are >C(CH₃)₂ ; Z is --CH₂ --CH₂ --; R¹ isunsubstituted thienyl; R², R⁵ and R⁶ are hydrogen; and R⁴ is hydrogen oralkyl or alkoxy having up to 10 carbon atoms.
 12. The method of claim10, wherein the compound employed is selected from the group consistingof 2-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiophene and3-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]thiopene.